Eric Jonasch, MD, shares pooled safety data on belzutifan in advanced RCC

In this video, Eric Jonasch, MD, highlights the background and key findings from the study, “In-depth characterization of the safety profile of belzutifan monotherapy in patients with renal cell carcinoma: A pooled analysis of four clinical trials,” which was presented at the Society of Urologic Oncology 25th Annual Meeting in Dallas, Texas. Jonasch is a professor of genitourinary medical oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas.

Video Transcript:

Belzutifan is a recently approved agent which blocks HIF-2α,hypoxia-inducible factor-2α, to prevent downstream transcription. This drug was FDA approved in 2021 for von Hippel-Lindau disease, and more recently, in December of 2023 in the US for advanced renal cell carcinoma for individuals who had progressed on an IO therapy plus a TKI. The purpose of this poster was to look at the toxicity profile, and it aggregated 4 studies that have been done over the past several years with belzutifan both in individuals with von Hippel-Lindau disease as well as in advanced renal cell carcinoma. [We] really asked the question, what do we know now with regards to toxicity? This drug does have some very specific toxicities: anemia, hypoxia, and fatigue. The ones that we were particularly interested in were the anemia and the hypoxia. The questions that we included were time to onset; How long did it take for this to happen? What was done about it? And, how did people do overall?

We did see that there was a certain percentage of individuals who had to have dose holding, and a smaller percentage of people had to have dose reduction, in general. Specifically for the anemia, close to 30%, about 28%, of people had grade 3 anemia. Of those individuals, a bit more than 20% ended up getting erythropoiesis-stimulating agents [ESAs]. A smaller percentage of individuals got blood transfusions, and a certain percentage got both. So, we saw definitely not the majority of individuals, but a distinct minority of individuals that needed to have some measures there to address these.

This is important in that the guidance on the package insert at this point in time suggests that you should be dose reducing only when hemoglobins drop to a certain level, and you are dose holding. The use of ESAs and transfusions is not recommended. But in the community, we are seeing that ESA use is quite high, as it was in the clinical trial. Secondly, the hypoxia occurred in about 16% of patients, and about 12% had great 3 hypoxia. That sounds a little scary, but that's an oxygen saturation of 89% or lower. So, it's not that low. And about 70% of individuals on the trial did get supplemental oxygen. In terms of the practice guidelines that we generally recommend here would be to hold the drug and wait till the oxygen saturation goes up; the half-life of the drug's only about a day, so it can go up fairly easily, and then dose reduce. Forcing or committing individuals to being on long-term oxygen is probably not a practical thing. That's really the upshot of this. There weren't any surprises, but it did provide us a fairly large—this is close to 600 individuals—data set where we could really look at the kinetics of the toxicities of the agent.

This transcript was AI generated and edited by human editors for clarity.